Linked Life Data

15118837

Source:http://linkedlifedata.com/resource/pubmed/id/15118837

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-2
pubmed:abstractText
Multidrug resistance associated proteins (MRPs) and P-glycoprotein (P-gp) are involved in hepatobiliary transport of various compounds. Our aim was (1) to define transporter specificity of the cholescintigraphic agents 99mTc-HIDA and 99mTc-MIBI, which are used clinically for myocardial perfusion measurements; and (2) to deduce MRP and P-gp functions in vivo from hepatic 99mTc kinetics. Accumulation of radioactivity was measured in the human tumor cell lines GLC4, GLC4/ADR150x (MRP1-overexpressing/P-gp-negative) and GLC4/P-gp (P-gp-overexpressing). Bile secretion was quantified in untreated and in glutathione-depleted control and MRP2-deficient (GY/TR-) rats. Hepatobiliary transport was measured using a gamma camera in both types of rats. 99mTc-HIDA accumulated 5.8-fold less in GLC4/ADR150x calls than in GLC4 or GLC4/P-gp cells. In GLC4/ADR150x, the cellular 99mTc-HIDA content was increased 3.4-fold by the MRP1,2 inhibitor MK571 (50 microM), while MK571 had no measurable effect in GLC4 and GLC4/P-gp cells. 99mTc-MIBI accumulated less in GLC4/P-gp and GLC4/ADR150x cells than in GLC4 cells. Bile secretion of 99mTc-HIDA was impaired in GY/TR- compared to control rats and not affected by glutathione depletion in GY/TR- rats. Hepatic secretion of 99mTc-HIDA was slower in GY/TR- (t1/2 40 min) than in control rats (t1/2 7 min). Bile secretion of 99mTc-MIBI was similar in both rat strains and impaired by glutathione depletion in control rats only, indicating compensatory activity of additional transporter(s) in GY/TR- rats. 99mTc-HIDA is transported only by MRP1,2 only, while 99mTc-MIBI is transported by P-gp and MRP1,2. The results indicate that hepatic P-gp and MRP1,2 function can be assessed in vivo by sequential use of both radiopharmaceuticals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
In vivo imaging of hepatobiliary transport function mediated by multidrug resistance associated protein and P-glycoprotein.
pubmed:affiliation
PET Center, University Hospital Groningen, The Netherlands. n.h.hendrikse@pet.azg.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't